Single-Cell RNA Sequencing and Microarray Analysis Unveiling the Role of Glucose Metabolism-Related Genes and Cellular Immune Infiltration in Preeclampsia: Identification of Novel Biomarkers

Abstract Preeclampsia (PE), a hypertensive disorder during pregnancy, is implicated in various complications such as fetal growth restriction and renal damage. Its pathogenesis is attributed to multiple factors including impaired trophoblast invasion, oxidative stress, and systemic inflammatory response. Additionally, the role of immune cell infiltration and glucose metabolism is crucial in PE's development. This study employed single-cell RNA sequencing data from publicly available databases to investigate the cellular mechanisms underlying PE. We identified glucose metabolism-related genes (GMRG) in relation to PE and discerned five unique cell types, predominantly Monocytes and NK cells, highlighting their potential role in PE's pathogenesis. Our study revealed an enriched gene distribution associated with glucose metabolism in these cells. Through the analysis of Differentially Expressed Genes (DEGs), we delineated 620 distinct genes. Notably, 13 of these genes, derived from the intersection of GMRG and DEGs, exhibited a pronounced association with PE. Molecular patterns further stratified PE samples based on 13 intersection genes, revealing a possible correlation between PE and CD8 T cells. Using Weighted Gene Co-expression Network Analysis (WGCNA), one major modules demonstrated strong associations with PE. In-depth analysis identified two potential biomarkers for PE diagnosis, CHPF and G6PC3, which exhibited enhanced expression in PE patients. Both genes are associated with glucose metabolism, with CHPF playing a role in chondroitin sulfate biosynthesis and G6PC3 involved in insulin resistance, an integral aspect of PE pathogenesis. Through qPCR and IHC analyses, we found significantly elevated expression and protein levels of CHPF and G6PC3 in PE tissues compared to normal samples, indicating their potential roles in PE.